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PMID: 16424906 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Skeletal muscle specification by myogenin and Mef2D via the SWI/SNF ATPase Brg1.

The EMBO journal ·Vol. 25 ·No. 3 ·2006-02-08 ·Pages 490-501

Ohkawa Y, Marfella CG, Imbalzano AN

Abstract

Myogenin is required not for the initiation of myogenesis but instead for skeletal muscle formation through poorly understood mechanisms. We demonstrate in cultured cells and, for the first time, in embryonic tissue, that myogenic late genes that specify the skeletal muscle phenotype are bound by MyoD prior to the initiation of gene expression. At the onset of muscle specification, a transition from MyoD to myogenin occurred at late gene loci, concomitant with loss of HDAC2, the appearance of both the Mef2D regulator and the Brg1 chromatin-remodeling enzyme, and the opening of chromatin structure. We further demonstrated that ectopic expression of myogenin and Mef2D, in the absence of MyoD, was sufficient to induce muscle differentiation in a manner entirely dependent on Brg1. These results indicate that myogenin specifies the muscle phenotype by cooperating with Mef2D to recruit an ATP-dependent chromatin-remodeling enzyme that alters chromatin structure at regulatory sequences to promote terminal differentiation.

MeSH Terms
Adenosine Triphosphate/metabolism Animals Cell Differentiation Cell Line Chromatin Assembly and Disassembly DNA Helicases Female Gene Expression Regulation, Developmental Histone Deacetylase 2 Histone Deacetylases/metabolism MEF2 Transcription Factors Mice Mice, Inbred C57BL Muscle Development/physiology Muscle, Skeletal/cytology,embryology,metabolism MyoD Protein/metabolism Myogenic Regulatory Factor 5/metabolism Myogenic Regulatory Factors/metabolism,physiology Myogenin/physiology Nuclear Proteins/metabolism,physiology Repressor Proteins/metabolism Transcription Factors/metabolism,physiology
Chemicals
MEF2 Transcription Factors Mef2d protein, mouse Myf5 protein, mouse MyoD Protein MyoD1 myogenic differentiation protein Myogenic Regulatory Factor 5 Myogenic Regulatory Factors Myogenin Nuclear Proteins Repressor Proteins Transcription Factors Adenosine Triphosphate Hdac2 protein, mouse Histone Deacetylase 2 Histone Deacetylases Smarca4 protein, mouse DNA Helicases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ohkawa Yasuyuki
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Marfella Concetta G A
Imbalzano Anthony N
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
2006-02-08
Epub
2006-00-19
Pages
490-501
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1383528
Subset
IM
Grants
NIGMS NIH HHS · R01 GM056244 · United States
NIGMS NIH HHS · GM56244 · United States
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